European Journal of Pharmacology, 62 (1980) 81--88 81 © Elsevier/North-Holland Biomedical Press ELECTROPHYSIOLOGICAL EFFECTS OF BUNAPHTINE ON ISOLATED RAT ATRIA JUAN TAMARGO Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid-3, Spain Received 1 October 1979, accepted 6 December 1979 J. TAMARGO, Electrophysiological effects of bunaphtine on isolated rat atria, European J. Pharmacol. 62 (1980) 81--88. The effects of a new antiarrhythmic, bunaphtine, on the electrical and mechanical activity of isolated rat atria were compared with those of quinidine and amiodarone. Both electrically stimulated and spontaneously beating atria were used. In spontaneously beating double atria bunaphtine produced a dose-dependent decrease in the rate, contractile force, work index and maximum following frequency at which the atria could respond to electri- cal stimulation, depressed the pacemaker activity and increased the sinus node recovery time. In isolated left atria bunaphtine prolonged the effective refractory period and decreased atrial excitability. Bunaphtine did not block positive chronotropie and inotropic responses to isoprenaline and did not reduce the positive inotropic effect of raised calcium concentrations. These results support the hypothesis that bunaphtine exerted on isolated atria a direct cardiodepressant effect similar to that of quinidine, and that it may be classified as a class 1 antiarrhythmic according to the classification of Vaughan Williams. Contractile force Bunaphtine Rat atria Atrial rate Excitability Refractory period 1. Introduction Bunaphtine (N-(2<liethylaminoethyl)-N-(n- butyl)-a-naphtamide) is a new antiarrhyth- mic drug which has been found effective in treating or preventing both ventricular and supraventricular arrhythmias (Botti, 1972; Vegis, 1975). Good results have been also ob- tained in patients with acute myocardial infarction (Botti et al., 1976). In spite of the interest in the use of butaphtine, conflicting results permit no conclusion concerning the mechanism of its antiarrhythmic action. There are four main ways in which most antiarrhythmic drug may act (Vaughan Wil- liams, 1970; Singh and Vaughan Williams, 1972). Class 1 action includes drugs which interfere with the fast inward sodium channel (membrane stabilizers); class 2 action, those with antisympathetic activity; class 3 action, those which prolong the cardiac action poten- tial; and finally, class 4 action, which includes those antiarrhythmics that interfere with the slow calcium inward current. On the basis of its electrophysiological properties, bunaphtine was initially classified as a membrane stabi- lizer (Ferroni and Monticelli, 1973) and was included in the class 1 antiarrhythmics of Vaughan Williams. However, Fenici et al. (1977) in recent experiments with human atria and using bipolar suction electrodes con- cluded that bunaphtine showed class 3 action. The present study was undertaken to deter- mine whether bunaphtine exhibited any one of these four mechanisms of action is isolated rat atria. To determine whether class 1 or class 3 action was exhibited, the effects of bunaph- tine were Compared to those induced by quinid~e and amiodarone, respectively. For class 2 or class 4 action, the effects of bun- aphtine on the responses induced by isopre- naline and calcium chloride were also studied.